This proposal is a collaborative, multidisciplinary program involving researchers from the College of Engineering, School of Medicine at the University of Washington and the Clinical Research Division at the Fred Hutchinson Cancer Research Center. The objective is to develop a high-quality fiber-optic imaging needle that can be integrated with a biopsy needle for in situ guidance of tissue sampling. New methods will be explored to control and achieve desired imaging beam parameters, and to simplify the microfabrication process. The imaging needle is not intended to replace the conventional needle biopsy and histology, but rather to optimize tissue sampling by directing the biopsy to areas of highest yield. Cancers develop over a period of several years and they are characterized by changes in tissue and cellular structure and tissue optical properties. Biopsy followed by histology is the current standard for cancer diagnosis. The major challenge with the gold standard is that biopsies can have low sensitivity due to sampling error. It remains challenging to target the biopsy needle to a small lesion or the most malignant tissue of a large lesion even under conventional image-guidance. Optical coherence tomography (OCT) is an emerging technology that can perform in vivo cross-sectional imaging of tissue microanatomy in real time. In addition, quantitative information about localized tissue optical properties can also be obtained with OCT. The hypothesis of this proposal is that a robust, miniature OCT imaging needle which provides high-resolution tissue microanatomy and quantitative localized tissue optical properties, can be developed and integrated within a biopsy needle for guiding biopsy in situ. The specific aims are to: (1) develop a miniature imaging needle using new engineering methods to achieve high optical quality and mechanical robustness; (2) integrate the imaging needle with a biopsy needle and test the performance of the integrated device with tissue phantoms; and (3) explore the feasibility of the integrated device for guiding biopsy in the mouse prostate cancer TRAMP model in vivo. If successful, the functionally integrated biopsy device can benefit tumor diagnosis in solid organs such as the breast, prostate and pancreas by reducing random sampling errors, minimizing the required sampling tissue volume and the total number of biopsies, and making biopsy less invasive. [unreadable] [unreadable] [unreadable]